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Th1133 details
Primary information
ID10643
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated.
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7306799
Date of Issue12-Nov-2007
Date of Expiry23-05-2020
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameEylea
CompanyRegeneron Pharmaceuticals
Brand DescriptionRegeneron Pharmaceuticals
Prescribed ForNeovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Central Retinal Vein Occlusion (CRVO)
Chemical NameNA
FormulationEYLEA is supplied as a preservative-free, sterile, aqueous solution in a single-use, glass vial designed to deliver 0.05 mL (50 microliters) of EYLEA (40 mg/mL in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose, pH 6.2).
Physical Appearance EYLEA is a sterile, clear, and colorless to pale yellow solution.
Route of AdministrationIntravitreal Injection
Recommended DosageThe recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
Contraindicationocular or periocular infections, active intraocular inflammation, Hypersensitivity
Side EffectsEndophthalmitis and retinal detachments, Increased intraocular pressure, Thromboembolic events
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID10644
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7531173
Date of Issue5-Dec-2009
Date of Expiry2-Feb-2026
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameZaltrap
CompanySanofi and Regeneron Pharmaceuticals, Inc.
Brand DescriptionSanofi and Regeneron Pharmaceuticals, Inc.
Prescribed Formetastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen
Chemical NameNA
FormulationZALTRAP is supplied in single-use vials of 100 mg per 4 ml and 200 mg per 8 ml formulated as 25 mg/mL ziv-aflibercept in polysorbate 20 (0.1%), sodium chloride (100 mM), sodium citrate (5 mM), sodium phosphate (5 mM), and sucrose (20%), in Water for Injection USP, at a pH of 6.2.
Physical Appearance ZALTRAP is a sterile, clear, colorless to pale yellow, non-pyrogenic, preservative-free, solution for administration by Intravenous infusion.
Route of AdministrationIntravenous infusion
Recommended Dosage4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks.
ContraindicationNA
Side EffectsHemorrhage, Gastrointestinal, Compromised Wound Healing, Fistula Formation, Hypertension, Arterial Thromboembolic Events, Proteinuria, Neutropenia and Neutropenic Complications, Diarrhea and Dehydration, Reversible Posterior Leukoencephalopathy Syndrome
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID10645
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7374758
Date of Issue20-05-2008
Date of Expiry23-05-2020
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1NA
Useful Link 2NA
RemarksNA


Primary information
ID10646
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7608261
Date of Issue27-10-2009
Date of Expiry14-06-2027
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1NA
Useful Link 2NA
RemarksNA


Primary information
ID10647
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7070959
Date of Issue7-Apr-2006
Date of Expiry23-05-2020
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1NA
Useful Link 2NA
RemarksNA


Primary information
ID10648
Therapeutic IDTh1133
Protein NameAflibercept
Sequence>Th1133_Aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight115000
Chemical FormulaC4318H6788N1164O1304S32
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeIntravitreal half life - 7.13 days
DescriptionAflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated
Indication/DiseaseThe opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
PharmacodynamicsCompared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Mechanism of ActionAblibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
ToxicityFor all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
MetabolismBecause aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
AbsorptionIn patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
After intravenous injection of aflibercept, the volume of distribution is 6 L.
ClearanceWhen cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
CategoriesAntineoplastic Agents and Ophthalmics
Patents NumberUS7374757
Date of Issue20-05-2008
Date of Expiry23-05-2020
Drug InteractionNA
TargetVascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1NA
Useful Link 2NA
RemarksNA